The following are key points to remember from this review article about antithrombotic therapy in peripheral artery disease (PAD):

Atherosclerotic cardiovascular disease affects more than 200 million adults worldwide. Lower extremity PAD is associated with significant morbidity and mortality; 5-10% of PAD patients will have recurrent events each year.

Patients with PAD have an elevated risk of cardiovascular death, myocardial infarction (MI), and stroke. The annual risk of cardiovascular death, MI, or hospitalization is 21%. The annual risk of major adverse limb events varies from 2-10% based on age, symptom classification, concomitant medical therapy, and prior revascularization procedures.

In the United States, medical treatment of PAD has traditionally involved antiplatelet monotherapy (either aspirin or clopidogrel), which is associated with an estimated 25% risk reduction in major vascular events (American Heart Association/American College of Cardiology lower extremity PAD guideline Class I, Level of Evidence A recommendation).

Despite being considered a “coronary artery disease (CAD) risk equivalent,” the use of antiplatelet and statin medications is significantly lower among PAD patients as compared to patients with CAD. Clinicians and health centers are encouraged to improve medical therapy rates, using techniques such as population health queries, audit and feedback, and other quality improvement or learning health system methods.

In patients with symptoms despite background medical therapy, cilostazole and supervised exercise training have been associated with improvements in walking distance and quality of life. There are few proven medical therapies for patients with critical limb ischemia, where the mortality rate is nearly 50% at 1 year.

Vorapaxar is a protease-activated receptor-1 (PAR-1) inhibitor that has been shown to reduce cardiovascular death, MI, or stroke by 1.2% (11.3% vs. 11.9% with placebo, hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.78-1.14). Despite lower risk of hospitalization, there was an increase in moderate and severe bleeding associated with vorapaxar use.